The reaction of imidazoles containing an aryl group at the 2-position with formaldehyde was reported by J. W. Cornforth and H. T. Huang in Journal of the Chemical Society 1948, page 733, and it was stated that the reaction was unsuccessful.
We have now found that when an imidazole not containing an aryl group at the 2-position was reacted with formaldehyde, the formaldehyde adds to the imino nitrogen atom at the 1-position of the imidazole ring to give unstable 1-hydroxymethylimidazole (i.e., N-methylol imidazole), but that an imidazole containing an aryl group at the 2-position reacts with formaldehyde to afford stable C-methylol imidazole in which the formaldehyde adds to the carbon atom of the imidazole ring.
The reaction between the imidazole not containing an aryl group at the 2-position and formaldehyde is schematically shown as follows: ##STR1## wherein R.sub.2 represents, for example, a hydrogen atom or an alkyl or benzyl group, and R.sub.4 represents, for example, a hydrogen atom or an alkyl or phenyl group.
As shown above, in the reaction of the imidazole not containing an aryl group at the 2-position with formaldehyde, the formaldehyde adds to the NH group at the 1-position to give an N-methylol derivative. The N-methylol derivative is unstable, and when allowed to stand in air, spontaneously decomposes to the imidazole while releasing formaldehyde. Furthermore, it decomposes by the action of water (or acidic water) to afford an aqueous solution of formaldehyde and the imidazole. For example, attempt to acetylate its hydroxyl group with acetic anhydride fails to give the desired acetyl ester because decomposition occurs first. Only the reaction of it with phenyl isocyanate can give stable phenyl urethane.
Examples of the N-methylol derivative are as follows:
1-Methylol imidazole: PA0 1-Methylol-2-methyl imidazole: PA0 1-Methylol-2-ethyl imidazole: PA0 1-Methylol-2,4(5)-dimethyl imidazole: PA0 1-Methylol-2-ethyl-4(5)-methyl imidazole:
Melting point, 58.degree.-59.degree. C. (acetone),
.nu.C-O, 1065 cm.sup.-1
Melting point of phenylurethane prepared therefrom, 167.degree.-168.degree. C. (acetone),
Melting point, 95.5.degree.-96.5.degree. C. (acetone),
.nu.C-O, 1065 cm.sup.-1
Melting point of phenylurethane prepared therefrom, 161.degree.-162.degree. C. (benzene),
Melting point, 73.degree.-74.degree. C. (acetone),
.nu.C-O 1048, 1075 cm.sup.-1,
Melting point of phenylurethane prepared therefrom, 141.degree.-142.degree. C. (benzene),
Melting point 108.degree.-109.degree. C. (acetone),
.nu.C-O, 1070 cm.sup.-1,
Melting point of phenylurethane prepared therefrom, 155.degree.-156.degree. C. (acetonitrile),
Melting point, 85.degree.-86.degree. C. (acetone),
.nu.C-O, 1060 cm.sup.-1,
Melting point of phenylurethane prepared therefrom, 129.5.degree.-130.5.degree. C. (acetone).
In view of the above experimental results, it is surprising that when an imidazole containing an aryl group at the 2-posttion is reacted with formaldehyde in a reaction medium having a pH of at least 7, the formaldehyde adds to the carbon atom of the imidazole ring to afford C-methylol imidazole, and the resulting C-methylol imidazole is a very stable compound.